Solvent-Dependent Enantiodivergence in anti-Selective Catalytic

Apr 17, 2019 - anti-Selective catalytic asymmetric nitroaldol reactions of α-keto esters promoted by a heterogeneous Nd/Na heterobimetallic catalyst ...
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Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

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Solvent-Dependent Enantiodivergence in anti-Selective Catalytic Asymmetric Nitroaldol Reactions Tomoya Karasawa, Akira Saito, Naoya Kumagai,* and Masakatsu Shibasaki* Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan

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ABSTRACT: anti-Selective catalytic asymmetric nitroaldol reactions of α-keto esters promoted by a heterogeneous Nd/ Na heterobimetallic catalyst exhibited a significant, unexpected disparity in enantioselection that was solvent-dependent. This phenomenon exclusively occurred when the stereogenic center of a diamide ligand had the smallest substituent (Me group, derived from L-Ala), which behaved uniquely in comparison with other structurally similar ligands to provide antipodal products under otherwise identical conditions. The impact of the substituent on diamide ligand 1 was first examined in the anti-selective nitroaldol reaction of α-keto ester 2a with nitroethane 3a (Table 1).12,15 The Nd/Na heterobimetallic catalyst was readily prepared by mixing ligand 1/NdCl3·6H2O/NaOtBu (1/1/6 ratio) in THF/nitroethane, which self-assembled to give an insoluble complex isolated by centrifugation. The catalyst prepared from archetypal L-Leuderived diamide ligand 1a (R = iBu) furnished the antinitroaldol (−)-(2R,3S)-4aa with 95% ee (97% yield) (entry 1). On the other hand, the reaction using L-Ala-derived ligand 1b (R = Me) under otherwise identical conditions provided the antipodal (+)-(2S,3R)-4aa with 75% ee (99% yield) (entry 2). As shown in entries 3−8, 1b is an outlier and other ligands having a substituent larger than the Me group exhibited the identical tendency to 1a, preferentially affording (−)-(2R,3S)4aa with low to modest enantioselectivity. The failed reactions with ligands 1i and 1j are likely due to incomplete selfassembly to give a heterogeneous catalyst (entries 9, 10). Given the heterogeneity and polymeric nature of the catalyst, the opposite enantioselectivity achieved with ligand 1b might be relevant to supramolecular chirality that can be leveraged by the chemical environment. This idea led us to screen solvents using ligand 1b.16 Generally, this intensively studied catalytic system prefers ethereal solvents to efficiently promote the reaction (Table 2). Intriguingly, commonly used cyclic ether solvents with similar physicochemical properties, THF and 2-Me-THF, promoted the reaction with divergent enantioselectivity (THF for (+)-4aa; 2-Me-THF for (−)-4aa), although the enantioselectivity was low when using 2-Me-THF (entries 1, 2). Whereas 2,5-Me2-THF and symmetric acyclic ethers failed to boost the enantioselectivity (entries 3−5), 4Me-THP, bidentate ether, and unsymmetrical acyclic ether gave (−)-4aa with greater than 50% ee (entries 6−9). In

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he nitroaldol reaction is a synthetically advantageous carbon−carbon bond-forming reaction that produces vicnitroalkanols from readily available starting materials under proton transfer conditions.1,2 In particular, catalytic asymmetric variants offer streamlined access to chiral building blocks frequently used for synthesizing pharmaceuticals. We developed the first catalytic asymmetric nitroaldol reaction with nitromethane using heterobimetallic complex LLB (LaLi3-tris(1,1′-bi-2-naphthoxide)) as an asymmetric catalyst in 1992,3 which later also proved effective for syn-selective and enantioselective reactions.4,5 To achieve anti-diastereoselectivity, we disclosed a distinct Nd/Na heterobimetallic complex utilizing a diamide ligand prepared from α-amino acids.6−8 The defining characteristic of the Nd/Na heterobimetallic catalyst is its heterogeneity, which expands the practical applicability of this asymmetric catalyst in continuous-flow reaction platforms. At the initial disclosure, NdO1/5(OiPr)13/5, an expensive Nd salt with limited availability, was indispensable as the basic Nd source for catalyst preparation. We recently overcame this limitation, however, by developing an alternative catalyst preparation protocol from inexpensive NdCl3·6H2O and NaOtBu,9,10 allowing for further application of this heterobimetallic catalyst to other electrophiles, e.g., trifluoromethyl ketones11 and α-keto esters,12 for the construction of tetrasubstituted stereogenic centers. In our continuing studies of the utility of this catalytic system, we observed an unexpected ligand effect with a significant disparity in enantioselectivity depending on the minute structure of the diamide ligand and reaction solvents. In this letter, we report that the catalyst prepared from L-Ala is capable of producing both enantiomers depending on the selected solvent.13 Given that the best solvent for each enantiomer is a common ethereal solvent (THF and MTBE (tert-butyl methyl ether)),14 the present enantiodivergent catalysis offers dual access to both enantiomers of synthetically useful chiral building blocks using the ligand derived from less expensive natural L-amino acids. © XXXX American Chemical Society

Received: March 20, 2019

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DOI: 10.1021/acs.orglett.9b00982 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Table 1. Screening of Chiral Ligands

Table 2. Screening of Solvents

entry

ligand

selfassemblyc

productd (4aa)

yielde (%)

anti/ syne

%eef (anti)

1 2 3 4 5 6 7 8 9 10

1a 1b 1c 1d 1e 1f 1g 1h 1i 1j

++ ++ ++ + ++ ++ ++ + − −

(−) (+) (−) (−) (−) (−) (−) (−) − −

97 99 84 97 99 99 99 31 trace trace

>98/2 >98/2 94/6 92/8 96/4 95/5 94/6 90/10 − −

95 75 41 33 72 56 0 5 − −

entry

solventb

productc (4aa)

yieldd (%)

anti/ synd

%eee (anti)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

THF 2-Me-THF 2,5-Me2-THF Et2O i Pr2O 4-Me-THP DME CPME MTBE toluene EtOAc i PrOAc CH2Cl2 EtCN DMF

(+) (−) (−) (−) (+) (−) (−) (−) (−) (−) (−) (−) (−) (−) −

99 99 97 99 66 96 89 99 97 79 88 74 96 30 trace

>98/2 >98/2 96/4 94/6 93/7 97/3 97/3 97/3 97/3 94/6 96/4 96/4 84/16 87/13 −

75 20 26 35 2 55 65 50 70 67 31 54 70 49 −

a 2a, 0.12 mmol; 3a, 1.2 mmol. b2,5-Me2-THF: 2,5-dimethyltetrahydrofuran (mixture of isomers). 4-Me-THP: 4-methyltetrahydropyran. CPME: cyclopentyl methyl ether. MTBE: tert-butyl methyl ether. c Optical rotation. dDetermined by 1H NMR analysis. eDetermined by chiral HPLC analysis.

a

2a, 0.12 mmol; 3a, 1.2 mmol. bThe absolute configuration of nitroaldol product 4aa was determined by comparing its chiral HPLC retention time with published data.12 cAmount of precipitation by self-assembly; (++) high, (+) moderate, (−) low. dOptical rotation. e Determined by 1H NMR analysis. fDetermined by chiral HPLC analysis.

Scheme 1. Scope and Limitations of Substratesa

particular, the use of MTBE (entry 9) gave (−)-4aa with 70% ee (97% yield) (entry 9). Non-Lewis basic apolar solvents such as toluene and CH2Cl2 also afforded moderate enantioselectivity, but less satisfactory diastereoselectivity and chemical yield (entries 10 and 13). The origin of the unusual disparity in enantioselectivity resulting from a minute difference in the solvent property is unclear at present, but the polymeric nature of the complex likely makes a partial contribution; only 1b having the smallest (Me) substituent exhibited the solventdependent enantiodivergency, which presumably resulted from supramolecular chirality sensitive to the chemical environment. Next, we examined the generality of the enantiodivergency with respect to the structure of α-keto ester 2 and nitroalkane 1 (Scheme 1). The divergent enantioselection which depended on the selected solvent (THF for (+)-4; MTBE for (−)-4) was maintained, although the degree of enantioselectivity fluctuated somewhat. The reactions using nitroethane 3a with αketo ester 2c (having a p-Me group) and 2f (having a p-Br group) afforded the highest enantioselectivity for (−)-4ca in MTBE and (+)-4fa in THF, respectively. In these cases, opposite enantiomers were obtained with slightly lower enantioselectivity, suggesting that the substrate structure partially influenced the enantiofacial preference. Enantiodivergency was observed even with nonaromatic substrate 2j, albeit with poor enantioselectivity. The structure of nitropropane 3b had a smaller effect on the enantioselection, and a similar level of enantiodivergency was observed for products 4ab and 4eb compared with the reactions using the identical α-keto esters and nitroethane 3a (for 4aa and 4ea).

a

Isolated yields of anti diastereomers are shown b2, 0.12 mmol; 3, 1.2 mmol. cRun with 1.5 mmol of 2a and 15 mmol of 3a. dRun at −78 °C for 48 h.

B

DOI: 10.1021/acs.orglett.9b00982 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

Org. Lett. 2009, 11, 5682. (f) Jin, W.; Li, X.; Wan, B. J. Org. Chem. 2011, 76, 484. (g) White, J. D.; Shaw, S. Org. Lett. 2012, 14, 6270. (h) Qin, D. D.; Yu, W.; Zhou, J. D.; Zhang, Y. C.; Ruan, Y. P.; Zhou, Z. H.; Chen, H. B. Chem. - Eur. J. 2013, 19, 16541. (i) Kaldun, J.; Prause, F.; Scharnagel, D.; Freitag, F.; Breuning, M. ChemCatChem 2016, 8, 1846. (6) Nitabaru, T.; Kumagai, N.; Shibasaki, M. Tetrahedron Lett. 2008, 49, 272. (7) (a) Nitabaru, T.; Nojiri, A.; Kobayashi, M.; Kumagai, N.; Shibasaki, M. J. Am. Chem. Soc. 2009, 131, 13860. (b) Nitabaru, T.; Kumagai, N.; Shibasaki, M. Angew. Chem., Int. Ed. 2012, 51, 1644. (c) Ogawa, T.; Kumagai, N.; Shibasaki, M. Angew. Chem., Int. Ed. 2013, 52, 6196. (d) Sureshkumar, D.; Hashimoto, K.; Kumagai, N.; Shibasaki, M. J. Org. Chem. 2013, 78, 11494. (e) Hashimoto, K.; Kumagai, N.; Shibasaki, M. Org. Lett. 2014, 16, 3496. (8) For selected examples of anti-selective catalytic asymmetric nitroaldol reactions, see: (a) Uraguchi, D.; Sakaki, S.; Ooi, T. J. Am. Chem. Soc. 2007, 129, 12392. (b) Handa, S.; Nagawa, K.; Sohtome, Y.; Matsunaga, S.; Shibasaki, M. Angew. Chem., Int. Ed. 2008, 47, 3230. (c) Sohtome, Y.; Kato, Y.; Handa, S.; Aoyama, N.; Nagawa, K.; Matsunaga, S.; Shibasaki, M. Org. Lett. 2008, 10, 2231. (d) Uraguchi, D.; Nakamura, S.; Ooi, T. Angew. Chem., Int. Ed. 2010, 49, 7562. (e) Lang, K.; Park, J.; Hong, S. Angew. Chem., Int. Ed. 2012, 51, 1620. (f) Xu, K.; Lai, G.; Zha, Z.; Pan, S.; Chen, H.; Wang, Z. Chem. - Eur. J. 2012, 18, 12357. (g) Li, Y.; Deng, P.; Zeng, Y.; Xiong, Y.; Zhou, H. Org. Lett. 2016, 18, 1578. (h) Blay, G.; Domingo, L. R.; HernandezOlmos, V.; Pedro, J. R. Chem. - Eur. J. 2008, 14, 4725. (i) Ube, H.; Terada, M. Bioorg. Med. Chem. Lett. 2009, 19, 3895. (j) Blay, G.; Hernández-Olmos, V.; Pedro, J. R. Org. Lett. 2010, 12, 3058. (k) Noole, A.; Lippur, K.; Metsala, A.; Lopp, M.; Kanger, T. J. Org. Chem. 2010, 75, 1313. (l) Qiong ji, Y.; Qi, G.; Judeh, Z. M. A. Eur. J. Org. Chem. 2011, 2011, 4892. (m) Boobalan, R.; Lee, G.-H.; Chen, C. Adv. Synth. Catal. 2012, 354, 2511. (n) Yao, L.; Wei, Y.; Wang, P.; He, W.; Zhang, S. Tetrahedron 2012, 68, 9119. (o) Arai, T.; Joko, A.; Sato, K. Synlett 2015, 26, 209. (9) Nonoyama, A.; Hashimoto, K.; Saito, A.; Kumagai, N.; Shibasaki, M. Tetrahedron Lett. 2016, 57, 1815. (10) The structure of the asymmetric catalyst has not been determined yet. (11) Karasawa, T.; Kumagai, N.; Shibasaki, M. Org. Lett. 2018, 20, 308. (12) Karasawa, T.; Oriez, R.; Kumagai, N.; Shibasaki, M. J. Am. Chem. Soc. 2018, 140, 12290. (13) Bartók, M. Chem. Rev. 2010, 110, 1663. (14) For a review of stereodivergent catalysis, see: (a) Beletskaya, I. P.; Nájera, C.; Yus, M. Chem. Rev. 2018, 118, 5080. (b) An intriguing reported example showing solvent-dependent enantiodivergence using an ethereal solvent: Nagata, Y.; Kuroda, T.; Takagi, K.; Suginome, M. Chem. Sci. 2014, 5, 4953. (15) For earlier examples of diastereoselective catalytic asymmetric nitroaldol reactions of α-keto esters, see: (a) Takada, K.; Takemura, N.; Cho, K.; Sohtome, Y.; Nagasawa, K. Tetrahedron Lett. 2008, 38, 1052. (b) Uraguchi, D.; Ito, T.; Nakamura, S.; Sakaki, S.; Ooi, T. Chem. Lett. 2009, 38, 1052. (16) The reaction of 2a with 3a in the presence of the an asymmetric catalyst derived from the diamide ligand 1a gave (−)-4aa with 2R and 3S in 85% ee (95% yield) in MTBE.

In conclusion, we report that a heterogeneous Nd/Na heterobimetallic catalyst displayed divergent enantioselectivity depending on the ethereal solvent selected, despite their similar physicochemical properties. Among the chiral diamide ligands tested, this solvent-dependent enantiodivergency was uniquely observed with an L-Ala-derived ligand possessing the smallest substituent at the stereogenic center. The supramolecular chirality of the polymeric heterogeneous catalyst is presumably responsible for the enantioselection; thus, the catalyst with the smallest intrinsic steric bias was capable of altering the fate of enantiodescrimination by a minute change in the chemical environment, i.e., ethereal solvents THF or MTBE. The enantiodivergency was valid for a range of substrates, indicating that the unusual divergent enantioselection was primarily driven by the polymeric catalyst. Structural investigation and mechanistic studies of the asymmetric induction, as well as improvement of the enantioselectivity, are currently underway.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b00982. Experimental procedures, spectroscopic data for new compounds, and NMR spectra (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Naoya Kumagai: 0000-0003-1843-2592 Masakatsu Shibasaki: 0000-0001-8862-582X Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was financially supported by KAKENHI (17H03025 and 18H04276 in Precisely Designed Catalysts with Customized Scaffolding) from JSPS and MEXT. We are grateful to Dr. Ryuichi Sawa, Ms. Yumiko Kubota, and Dr. Kiyoko Iijima at the Institute of Microbial Chemistry for NMR analysis.

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REFERENCES

(1) Henry, L. C. R. Hebd. Seances Acad. Sci. 1895, 120, 1265. (2) For reviews of asymmetric nitroaldol reactions, see: (a) Boruwa, J.; Gogoi, N.; Saikia, P. P.; Barua, N. C. Tetrahedron: Asymmetry 2006, 17, 3315. (b) Palomo, C.; Oiarbide, M.; Laso, A. Eur. J. Org. Chem. 2007, 2007, 2561. (c) Blay, G.; Hernández-Olmos, V.; Pedro, J. R. Synlett 2011, 2011, 1195. (3) Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem. Soc. 1992, 114, 4418. (4) Sasai, H.; Tokunaga, T.; Watanabe, S.; Suzuki, T.; Itoh, N.; Shibasaki, M. J. Org. Chem. 1995, 60, 7388. (5) For selected examples of syn-selective catalytic asymmetric nitroaldol reactions, see: (a) Sohtome, Y.; Hashimoto, Y.; Nagasawa, K. Eur. J. Org. Chem. 2006, 2006, 2894. (b) Arai, T.; Watanabe, M.; Yanagisawa, A. Org. Lett. 2007, 9, 3595. (c) Sohtome, Y.; Takemura, N.; Takada, K.; Takagi, R.; Iguchi, T.; Nagasawa, K. Chem. - Asian J. 2007, 2, 1150. (d) Arai, T.; Takashita, R.; Endo, Y.; Watanabe, M.; Yanagisawa, A. J. Org. Chem. 2008, 73, 4903. (e) Kim, H. Y.; Oh, K. C

DOI: 10.1021/acs.orglett.9b00982 Org. Lett. XXXX, XXX, XXX−XXX